Macrolides as Immunomodulatory Agents

Diffuse panbronchiolitis (DPB) is a disease characterized by diffuse bilateral centrilobular lesions consisting of peribronchial infiltration of inflammatory cells. More than 50 years after its first being reported in Japan, DPB is recognized as a disease that predominantly affects East Asians and disease susceptibility genes have been proposed. Kudo et al. found that low-dose long-term erythromycin (EM) therapy can be an effective treatment for DPB, resulting in a marked improvement in prognosis. The beneficial effect of EM therapy led to progress in understanding the pathogenesis of chronic inflammatory airway diseases and to new developments in the field of research on actions other than the antimicrobial activity of 14- and 15-membered ring macrolides. Macrolide therapy is most effective in the early stage of the disease and should be initiated as soon as possible. In case of exacerbation, infection with Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Pseudomonas aeruginosa should be considered, and effective antimicrobial agents should be administered. In recent years, the number of cases complicated by pulmonary nontuberculous mycobacterial infections has been increasing. In particular, the induction of clarithromycin resistance by Mycobacterium avium complex has become a problem. Macrolide-resistant DPB is also becoming a clinical problem.